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PPT
Collaborations
Johnson & Johnson has provided Drs. Audrey Odom John and Paul Hruz at Washington University in St. Louis (WUSTL) with its Jump-stARter library to screen against Plasmodium falciparum, the most deadly species of malaria parasite. Drs. Odom John and Hruz have developed a novel platform to selectively screen compounds’ ability to inhibit parasite glucose transport.
Dr. Stephen Ghogomu at the University of Buea has identified two proteins as potential biomarkers for adult-stage onchocerciasis. To support his diagnostic development, Dr. Jose Gomez-Marquez and Dr. Kimberly Hamad Schifferli at the Massachusetts Institute of Technology (MIT) have shared Ampli Blocks, a platform for diagnostic development. Dr. Ghogomu will use these blocks as a platform to develop an onchocerciasis diagnostic device.
The Ampli Block kit includes a set of 40 different building blocks that enable lab workers around the world to assemble them in different ways to produce diagnostic devices. By supplementing the engineering of diagnostic development, Ampli Blocks allow researchers to focus on the biochemistry of detection and promote independent development of site-specific diagnostic devices.
Artemisinin combination therapy (ACT) is the standard of care in treating uncomplicated malaria, while newer synthetic endoperoxides like artefenomel are being actively studied in clinical trials. Adam Renslo, in the Department of Pharmaceutical Chemistry at the University of California, San Francisco (UCSF), is exploring artefenomel-like trioxolane analogs bearing a novel substitution pattern that may deliver improved physiochemical properties. To assist the Renslo Lab in driving this program toward clinical candidate selection, Medicines for Malaria Venture (MMV) is supporting the Renslo Lab in assessing the solubility, lipophilicity, and metabolic stability of frontrunner compounds using appropriate in vitro ADME assays. The resulting data will be a key factor in the selection of the best analogs for further in vivo evaluation. Given the extent of work and progress in the endoperoxide area, new compounds will only be of interest if their pharmacokinetics and potency support very low single dose potential with no alteration of parasite clearance between sensitive and resistant parasites. These early studies will help to assess the Renslo Lab compounds against this high bar.
Dr. Audrey Odom John (Washington University in St. Louis) and Dr. Cynthia Dowd (The George Washington University) identified an antimalarial drug candidate with a novel, parasite-specific target. The investigators have explored various solutions to improve the compound’s pharmacokinetic properties, including administration in a patch formulation. BVGH coordinated a call between Dr. Odom John, Dr. Dowd, and a Pfizer scientist with expertise in transdermal drug delivery to help assess the feasibility of this approach for the compound.
A Pfizer scientist with expertise in transdermal drug delivery shared advice on the feasibility of a transdermal delivery for the investigators’ antimalarial drug candidate and helped suggest next steps for development.
In an effort to develop novel drugs against Chagas disease, Dr. Artur Cordeiro at the Brazilian Biosciences National Laboratory (LNBio) has identified chemical scaffolds that have shown activity against two promising targets and efficacy against the parasite’s intracellular form. In order to identify additional inhibitors or novel chemical scaffolds with activity against both Trypanosoma cruzi enzymes, Dr. Cordeiro will be working with Novartis as part of their Facilitated Access to Screening Technologies (FAST) Lab program to screen several of Novartis’ proprietary compounds against these two targets to identify tool compounds for structure-based drug discovery.
Leishmaniasis is endemic in nearly 100 countries worldwide, and with treatment failure a growing problem, there is an urgent need for development of novel first-line agents. Dr. Edmund Ekuadzi, co-manager of the Kwame Nkrumah University of Science and Technology (KNUST) Central Laboratory and former Novartis Next Generation Scientist Program fellow, is exploring the anti-leishmanial properties of Ghanaian plants used in traditional medicines. He will receive training in bioassay-guided fractionation of plant extracts through the Wellcome Centre for Anti-Infectives Research (WCAIR) program at the University of Dundee to advance his drug discovery programs.
University of Dundee will be providing expertise on fractionation and synthesis of small molecule compounds, as well as a bioassay for the fractionation of plant extracts. University of Dundee will be hosting Dr. Ekuadzi for a three-month fellowship, beginning in June.
Assets